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      Exercise Lowers Plasma Angiopoietin-Like 2 in Men with Post-Acute Coronary Syndrome

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          Abstract

          Pro-inflammatory angiopoietin-like 2 (angptl2) promotes endothelial dysfunction in mice and circulating angptl2 is higher in patients with cardiovascular diseases. We previously reported that a single bout of physical exercise was able to reduce angptl2 levels in coronary patients. We hypothesized that chronic exercise would reduce angptl2 in patients with post-acute coronary syndrome (ACS) and endothelial dysfunction. Post-ACS patients (n = 40, 10 women) were enrolled in a 3-month exercise-based prevention program. Plasma angptl2, hs-CRP, and endothelial function assessed by scintigraphic forearm blood flow, were measured before and at the end of the study. Exercise increased VO 2peak by 10% (p<0.05), but did not significantly affect endothelial function, in both men and women. In contrast, exercise reduced angptl2 levels only in men (-26±7%, p<0.05), but unexpectedly not in women (+30±16%), despite similar initial levels in both groups. Exercise reduced hs-CRP levels in men but not in women. In men, levels of angptl2, but not of hs-CRP, reached at the end of the training program were negatively correlated with VO 2peak (r = -0.462, p = 0.012) and with endothelial function (r = -0.419, p = 0.033) measured at baseline: better initial cardiopulmonary fitness and endothelial function correlated with lower angptl2 levels after exercise. Pre-exercise angptl2 levels were lower if left ventricular ejection time was long (p<0.05) and the drop in angptl2 induced by exercise was greater if the cardiac output was high (p<0.05). In conclusion, in post-ACS men, angptl2 levels are sensitive to chronic exercise training. Low circulating angptl2 reached after training may reflect good endothelial and cardiopulmonary functions.

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          Dose response between physical activity and risk of coronary heart disease: a meta-analysis.

          No reviews have quantified the specific amounts of physical activity required for lower risks of coronary heart disease when assessing the dose-response relation. Instead, previous reviews have used qualitative estimates such as low, moderate, and high physical activity. We performed an aggregate data meta-analysis of epidemiological studies investigating physical activity and primary prevention of CHD. We included prospective cohort studies published in English since 1995. After reviewing 3194 abstracts, we included 33 studies. We used random-effects generalized least squares spline models for trend estimation to derive pooled dose-response estimates. Among the 33 studies, 9 allowed quantitative estimates of leisure-time physical activity. Individuals who engaged in the equivalent of 150 min/wk of moderate-intensity leisure-time physical activity (minimum amount, 2008 U.S. federal guidelines) had a 14% lower coronary heart disease risk (relative risk, 0.86; 95% confidence interval, 0.77 to 0.96) compared with those reporting no leisure-time physical activity. Those engaging in the equivalent of 300 min/wk of moderate-intensity leisure-time physical activity (2008 U.S. federal guidelines for additional benefits) had a 20% (relative risk, 0.80; 95% confidence interval, 0.74 to 0.88) lower risk. At higher levels of physical activity, relative risks were modestly lower. People who were physically active at levels lower than the minimum recommended amount also had significantly lower risk of coronary heart disease. There was a significant interaction by sex (P=0.03); the association was stronger among women than men. These findings provide quantitative data supporting US physical activity guidelines that stipulate that "some physical activity is better than none" and "additional benefits occur with more physical activity."
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            The effects of physical activity on serum C-reactive protein and inflammatory markers: a systematic review.

            Physical activity is associated with a reduced incidence of coronary disease, but the mechanisms mediating this effect are not defined. There has been considerable recent interest in inflammation in the pathogenesis of cardiovascular disease. Some of the beneficial role of physical activity may result from its effects on the inflammatory process. We searched PubMed for articles published between 1975 through May 2004 using the terms exercise, physical activity, or physical fitness combined with C-reactive protein, inflammation, inflammatory markers, or cytokines. The review revealed 19 articles on the acute inflammatory response to exercise, 18 on cross-sectional comparisons of subjects by activity levels, and 5 examining prospectively the effects of exercise training on the inflammatory process. Exercise produces a short-term, inflammatory response, whereas both cross-sectional comparisons and longitudinal exercise training studies demonstrate a long-term "anti-inflammatory" effect. This anti-inflammatory response may contribute to the beneficial effects of habitual physical activity.
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              Physical activity and reduced risk of cardiovascular events: potential mediating mechanisms.

              Higher levels of physical activity are associated with fewer cardiovascular disease (CVD) events. Although the precise mechanisms underlying this inverse association are unclear, differences in several cardiovascular risk factors may mediate this effect. In a prospective study of 27,055 apparently healthy women, we measured baseline levels of hemoglobin A1c, traditional lipids (total, low-density lipoprotein, and high-density lipoprotein cholesterol), novel lipids [lipoprotein(a) and apolipoprotein A1 and B-100], creatinine, homocysteine, and inflammatory/hemostatic biomarkers (high-sensitivity C-reactive protein, fibrinogen, soluble intracellular adhesion molecule-1) and used women's self-reported physical activity, weight, height, hypertension, and diabetes. Mean follow-up was 10.9+/-1.6 years, and 979 incident CVD events occurred. The risk of CVD decreased linearly with higher levels of activity (P for linear trend or = 1500 kcal/wk of 27%, 32%, and 41%, respectively. Differences in known risk factors explained a large proportion (59.0%) of the observed inverse association. When sets of risk factors were examined, inflammatory/hemostatic biomarkers made the largest contribution to lower risk (32.6%), followed by blood pressure (27.1%). Novel lipids contributed less to CVD risk reduction compared with traditional lipids (15.5% and 19.1%, respectively). Smaller contributions were attributed to body mass index (10.1%) and hemoglobin A1c/diabetes (8.9%), whereas homocysteine and creatinine had negligible effects (< 1%). The inverse association between physical activity and CVD risk is mediated in substantial part by known risk factors, particularly inflammatory/hemostatic factors and blood pressure.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                13 October 2016
                2016
                : 11
                : 10
                : e0164598
                Affiliations
                [1 ]Montreal Heart Institute, Research Center, University of Montreal, Montreal, Quebec, Canada
                [2 ]Cardiac Rehabilitation and Prevention Center (EPIC) of the Montreal Heart Institute, University of Montreal, Montreal, Quebec, Canada
                [3 ]Departments of Pharmacology and Surgery, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada
                [4 ]Montreal Behavioral Medicine Centre, Montreal, Quebec, Canada
                [5 ]School of Public Health, University of Montreal, Montreal, Quebec, Canada
                Department of Cardiology and Angiology, GERMANY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: NTT CH DH JL ET A. Nigam.

                • Data curation: NTT.

                • Formal analysis: NTT JL.

                • Funding acquisition: MJ ET A. Nigam.

                • Investigation: NTT DH CY XL A. Nguyen JFL JL CH AA MG.

                • Methodology: DH CY XL A. Nguyen JFL JL MG ET.

                • Project administration: NTT JL.

                • Resources: ET Martin Juneau A. Nigam.

                • Supervision: ET A. Nigam.

                • Validation: NTT DH CH JL ET A. Nigam.

                • Visualization: NTT.

                • Writing – original draft: NTT ET.

                • Writing – review & editing: NTT MG JL ET A. Nigam.

                Author information
                http://orcid.org/0000-0001-5827-8935
                Article
                PONE-D-16-29919
                10.1371/journal.pone.0164598
                5063321
                27736966
                00de745d-789e-4731-aa39-eaeccde36c82
                © 2016 Thorin-Trescases et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 26 July 2016
                : 27 September 2016
                Page count
                Figures: 3, Tables: 3, Pages: 14
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100000028, Institute of Circulatory and Respiratory Health;
                Award ID: 14496
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100000028, Institute of Circulatory and Respiratory Health;
                Award ID: 133649
                Award Recipient :
                Funded by: Fondation Institut de Cardiologie de Montréal
                Award Recipient :
                Funded by: Fondation Institut de Cardiologie de Montreal
                Award Recipient :
                Funded by: Fondation EPIC
                Award Recipient :
                Funded by: Fondation EPIC
                Award Recipient :
                Funded by: Fondation EPIC
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100000038, Natural Sciences and Engineering Research Council of Canada;
                Award ID: Postgraduate scholarship
                Award Recipient :
                This work was supported by the Canadian Institutes of Health Research (grants number 14496 and 133649 to ET), the Foundation of the Montreal Heart Institute (ET, MJ, A Nigam) and EPIC Center Foundation (MJ, A Nigam). Carol Yu was supported by the Postgraduate Scholarship from the Natural Sciences and Engineering Research Council of Canada. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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